This application is directed to a diagnostic assay device and, more particularly, to a diagnostic assay device which allows retention of a fluid test sample applied to the assay device until it is desired to carry out its interaction with the test materials utilized to provide a detectable change.
Devices for use in diagnostic assays are known in the art, including devices which provide a luminescence readout signal as an indication of whether a particular analyte or metabolite is present in a test fluid. U.S. Pat. No. 3,390,962 discloses a biochemical test plate for the facile determination of the immunoprecipitation titer of an antigen-antibody reaction and for determining the antigenic similarities between several antigens when each is at its optimum concentration for the precipitin reaction. In operation, a constant concentration of antibody is disposed in troughs and serially diluted serum or antigen is placed individually into the cup-shaped depressions of the apertures, thereby measuring the immunodiffusion precipitin reaction over a concentration range.
U.S. Pat. No. 3,415,361 discloses a disposable test device and container therefor. The test device described therein includes a container in which pre-measured quantities of reactants for a chemical or immunological test are stored ready for use, with the container being adapted to provide a reaction vessel for the test and to permit observation of visible changes indicating the occurrence of and/or the extent of the reaction caused by the introduction thereinto of an aliquot sample of fluid to be tested, whereby tests can be carried out with a minimum of manipulative steps and supportive equipment.
U.S. Pat. No. 3,865,548 discloses an analytical apparatus for performing chemical analysis and, in particular, to small load operation biomedical test needs. The apparatus described therein comprises a cuvette having therein a first porous barrier which serves to compartmentalize the cuvette, and a first test reagent fluid in a first reagent compartment in the cuvette, the barrier being in direct contact therewith, a second porous barrier and a second test reagent fluid being present, the second test reagent being disposed in a second compartment on the side of the second barrier away from the first reagent compartment, the second barrier being in direct contact with the second test reagents.
U.S. Pat. No. 4,264,560 discloses a clinical analytical system which includes an arrangement for the chemical analysis of a small quantity of sample wherein a specimen of small size is passed through a porous distribution first medium onto a reagent-containing second medium. The reagent-containing second medium is a thin, flat, liquid-impervious medium. A reagent is encapsulated upon the second medium as a flat, liquid-phase surface. The first and second mediums are so arranged and disposed that when firmly pressed together, the encapsulated liquid reagent will be liberated and the specimen will be distributed through the first medium onto the liquid-phase liberated reagent where the subsequent reaction of the liquid-phase reagent and the specimen can then be identified by reading means.
U.S. Pat. No. 4,510,393 discloses a self-contained, portable photo chamber for photographically recording the extent of a chemical reaction such as in an immunological test, wherein a substrate emitting radiation such as gamma radiation is supported in facing contact with a film and with intensifying means, so that exposure time is reduced as a result of emission of further radiation such as a visible light from the intensifying means and its recording on the film.
U.S. Pat. No. 4,587,221 discloses a non-centrifugation/non-decantation method for carrying out specific binding assay tests, wherein liquid and solid phases are present. The device described therein consists of a mixing reservoir into which is fitted snugly a mixing separator having a channel in the vertical axis of the mixer separator. A rack holding a number of the mixing reservoirs containing the incubated reagents and analytes, capped with the mixer separators, is placed into a press-device designed to perform at a controlled rate a downward movement. The mixer separators are pushed downwards into the mixing reservoirs at a chosen rate for a preselected distance to complete the mass transport and separation operations. The separation devices are removed and either one of the separated phases can be measured in the desired analytical instrument for a quantitative or qualitative determination.
U.S. Pat. No. 4,797,259 discloses a diagnostic test device which includes a plate having at least one well, preferably a plurality of wells, each with an open bottom across which a composite membrane comprising three layers is placed, with a hydrophobic, liquid-tight seal provided at the periphery of the each well. The composite membrane from the top of the upstream side to the bottom or downstream side, in sequence, includes a first reaction or filtration layer formed from a thin, lipophilic, microporous membrane, a second or sealing layer, preferably a hydrophobic material in sheet or fiber form, such as nonwoven polypropylene fibers, and a liquophobic, preferably hydrophobic, barrier layer having one or more apertures which allows liquid to exit the well while eliminating lateral migration of a pendant liquid drop. The liquophobic seal provided by the liquophobic sealing layer eliminates xe2x80x9ccross-talkxe2x80x9d by lateral diffusion or wicking.
U.S. Pat. No. 5,035,866 discloses an apparatus for performing and measuring chemical reactions which includes a reaction test apparatus having reaction wells wherein reactants are controllably mixed, and exposure apparatus which receives and positions the reaction test apparatus adjacent a photographic film. Each of the reaction wells includes at least two reaction cups, arranged one above the other. The uppermost reaction cups have orifices in the bottoms, so that the liquid can be mixed and reacted in the uppermost cup, and then controllably transferred to the lower cup to be mixed with additional reactants. In a preferred embodiment, the reaction cups are supported in plates that are structurally integral with the cups, and are superimposed to make a test block. The test block is retained in the exposure apparatus, and liquid is forced from the upper cup to the lower cup by application of pressure to the top of the upper cup.
U.S. Pat. No. 5,418,171 discloses an apparatus for determining the presence or absence of a target analyte in a liquid sample, which comprises: a container capable of accommodating the liquid sample and having a transparent portion; and an insertion member which is capable of being inserted into the container and which comprises: a porous member which has a main surface and a reverse surface and which has on the main surface a substance capable of specifically binding to the target analyte; and an absorbent bonded to the reverse surface of the porous member; the porous member being supported in the insertion member whereby, when the insertion member is inserted into the container, the main surface can be observed from the outside of the container through the transparent portion of the vessel and the liquid sample is absorbed into the absorbent through the porous member.
U.S. Pat. No. 5,552,276 discloses a measuring apparatus for use in a binding assay to determine the presence or amount of an analyte in a fluid test sample through the use of a label capable of producing a detectable response, which comprises: a porous body having releasably attached thereto an agent soluble in the test sample; a liquid permeable porous reaction membrane disposed below the porous body having defined thereon at least one reaction area, the reaction area having immobilized thereon an affinity substance capable of directly or indirectly capturing the analyte or an agent soluble in the test sample to thereby produce the detectable response; an absorption member disposed below the liquid permeable porous membrane having an opening being positioned below the reaction area of the liquid permeable porous membrane to define a reaction solution storing space within the opening, the absorption member being, arranged so as to contact only a peripheral area of the liquid permeable porous membrane via an intervening liquid impermeable sheet; a liquid impermeable transparent cover disposed below the opening of the absorption member; and a liquid impermeable case accommodating the members and having a top surface adjacent the porous body and a bottom surface adjacent the transparent cover, the top surface having defined therein a top opening for introducing the fluid test sample, and the bottom surface having defined therein a bottom opening for observation of the detectable response.
The design and performance of such prior art diagnostic test elements, kits and processes in some settings is not completely satisfactory. For example, some of the known devices are very complicated, nonportable, systems which require a skilled operator to conduct the analyses. It would be desirable to have a diagnostic device which is capable of either manual use or usable with an apparatus having programmed instructions, which is portable and disposable, and which allows any user to conduct the test.
It would also be desirable to have a device which may be used at home and which enables the user, especially in the case of an elderly or physically-challenged person, to easily load a test sample into a diagnostic test element and to conduct a test to determine the presence of any particular target substance of interest and which, at the same time, provides a device which is relatively inexpensive and which is sturdy, safe and portable.
As the state of the art for diagnostic test elements and kits containing such novel elements continues to move forward, new techniques and materials continue to be developed by those of skill in the art in order to meet the performance criteria required of such diagnostic test elements devices and materials thereof, including the ease of home use, and the reliability and accuracy of the results provided therefrom.
These and other objects and advantages are obtained in accordance with the invention by providing a diagnostic assay device which includes a layer of a deformable material, a well for holding a fluid sample, a layer of a porous material and a diagnostic assay element spaced apart from the deformable material layer. The porous material forms the bottom surface of the fluid-holding well and is capable of preventing the fluid sample from passing through when the porous material is spaced apart from and out of contact with the diagnostic assay element.
In operation the fluid sample is deposited in the fluid-holding well and retained therein until it is desired to initiate the assay. To initiate the assay, the deformable material layer is deformed so as to bring at least a part of the porous material in contact with the diagnostic assay element whereby at least a portion of the fluid sample is caused to be delivered to the assay element. The assay element includes the reagent(s) necessary to carry out the analysis for the analyte or metabolite of interest. The presence of the analyte or metabolite of interest causes a detectable change to occur within the assay element. The detectable change developed within the assay element may be any of many known types utilized in analytical elements including colorimetric, fluorescent, chemiluminescent etc. Where the signal is fluorescent or chemiluminescent it may be captured by any of a variety of techniques including by exposing a photographic film material, which may be a self-developing photographic film, reading the signal generated with an optical readout system, etc. The detectable change, whether it is a color change which is to be evaluated visually or read spectrophotometrically or whether it is some other type of change such as the generation of a fluorescent or chemiluminescent output signal which is to be read out spectrofluorometrically or captured on a photographic film material or in a luminometer, will be analyzed over a specific portion of the assay element surface, typically a circular or rectangular area substantially in the center of the assay element. Thus, a generally uniform distribution of the fluid sample is provided throughout the area of the assay element which will be analyzed. The assay element may provide a qualitative or a quantitative result.
In a particularly preferred embodiment the diagnostic assay element incorporated in the assay device is a relatively thin film multilayer assay element. The assay device is particularly well suited for use with thin film multilayer diagnostic assay elements because these require only a relatively small volume of test fluid and the assay device is adapted to deliver to the assay element a volume of test fluid which matches the requirements of the assay element.
Deformation of the deformable material layer to initiate the assay can be carried out manually such as by the user applying a downward force to the deformable material layer or the assay device may be inserted into a holding apparatus which can be manipulated to cause the fluid sample to be delivered to the assay element to initiate the assay.